Supatporn Tepmongkol

Rosiglitazone Effect on Radioiodine Uptake in Thyroid Carcinoma Patients with High Thyroglobulin but Negative Total Body Scan: A Correlation with the Expression of Peroxisome Proliferator–Activated Receptor-Gamma

BACKGROUND Thyroid carcinoma patients with high thyroglobulin (Tg) level but negative total body scan (TBS) are difficult to treat with radioiodine (RAI). The objective of this study was to determine if treatment with rosiglitazone (RZ), a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, was associated with an increase in RAI uptake in thyroid carcinoma patients with high serum Tg and negative TBSs. We also determined if there was a correspondence between the effect of RZ and the degree of staining for PPAR-gamma within thyroid cancer tissues. METHODS We prescribed 8 mg of RZ daily for 6 weeks in 23 patients with epithelial cell thyroid carcinoma who previously had negative posttherapeutic I-131 total body scans (post Rx TBSs) with high serum Tg concentrations. Diagnostic total body scans (Dx TBSs) before and 6 weeks after RZ treatment were compared. An ablative dose of I-131 was then given to all patients, and post Rx TBS was performed to evaluate RAI uptake. Immunohistochemical staining of PPAR-gamma expression in thyroid cancer biopsies was done to correlate this with possible effects of RZ on RAI uptake. RESULTS Seven patients had strong PPAR-gamma-positive staining in thyroid biopsies, nine patients had weakly positive staining, and seven patients had negative staining. Five of seven patients with strong staining had either positive post Rx TBS, or both Dx TBS and post Rx TBS. One of nine patients with weak staining had positive Dx TBS and post Rx TBS. In contrast, none of the seven patients with negative staining had positive TBS. CONCLUSIONS RZ can increase RAI uptake in thyroid tissue in the majority of patients with epithelial cell thyroid carcinoma whose previous posttherapeutic I-131 scans were negative provided they have high intensity and extent of PPAR-gamma expression in thyroid tissue. Few, if any, patients with weak or no PPAR-gamma expression in thyroid cancer tissue increase RAI uptake after RZ treatment.

131I MIBG therapy in neuroblastoma: Mechanisms, rationale, and current status

131I MIBG has been used as palliative treatment of neuroblastoma patients with recurrent or persistent disease who failed other modalities of treatment. Since the results were promising, the concept arose of using it in conjunction with other modalities, either as an up-front treatment or as combination therapy. This article reviews the principle of 131I MIBG treatment, in conjunction with other modalities currently used for the treatment of neuroblastoma, in an attempt to improve the final outcome.

Comparative analysis of MR imaging, Ictal SPECT and EEG in temporal lobe epilepsy: a prospective IAEA multi-center study

Background and purposeMR imaging, ictal single-photon emission CT (SPECT) and ictal EEG play important roles in the presurgical localization of epileptic foci. This multi-center study was established to investigate whether the complementary role of perfusion SPECT, MRI and EEG for presurgical localization of temporal lobe epilepsy could be confirmed in a prospective setting involving centers from India, Thailand, Italy and Argentina.MethodsWe studied 74 patients who underwent interictal and ictal EEG, interictal and ictal SPECT and MRI before surgery of the temporal lobe. In all but three patients, histology was reported. The clinical outcome was assessed using Engel’s classification. Sensitivity values of all imaging modalities were calculated, and the add-on value of SPECT was assessed.ResultsOutcome (Engel’s classification) in 74 patients was class I, 89%; class II, 7%; class III, 3%; and IV, 1%. Regarding the localization of seizure origin, sensitivity was 84% for ictal SPECT, 70% for ictal EEG, 86% for MRI, 55% for interictal SPECT and 40% for interictal EEG. Add-on value of ictal SPECT was shown by its ability to correctly localize 17/22 (77%) of the seizure foci missed by ictal EEG and 8/10 (80%) of the seizure foci not detected by MRI.ConclusionsThis prospective multi-center trial, involving centers from different parts of the world, confirms that ictal perfusion SPECT is an effective diagnostic modality for correctly identifying seizure origin in temporal lobe epilepsy, providing complementary information to ictal EEG and MRI.

Outcome of temporal lobectomy for hippocampal sclerosis in older patients

Patients of 50 years or older account for a small but significant portion of the patient population that receives surgical treatment for epilepsy. There have been few studies reporting surgical outcomes from temporal lobectomy in older patients. We examined seizure outcome and surgical complications after anterior temporal lobectomy for temporal lobe epilepsy with pathological evidence of unilateral hippocampal sclerosis. Two patient groups were compared in this study: patients 50 years or older (mean age 55.5 years old, n=16) and patients less than 50 years old (mean age 32.9 years old, n=184). After a minimum of one year follow up, younger patients (79.4%, n=146) were significantly more likely to be seizure-free (p=0.041) compared to older patients (56.3%, n=9). There was no significant difference (p=0.404) between the two age groups in the percentage of patients withdrawn from medication following surgery. Surgical complications were significantly higher in the older age group compared to the younger age group (p=0.009), although there was no permanent morbidity. Thus, while surgical treatment of temporal lobe epilepsy with unilateral hippocampal sclerosis is still beneficial in older patients who are refractory to medical therapy, surgical treatment should be considered at as early an age as possible, to maximize the chance for a better outcome with fewer complications.

Factors affecting bilateral temporal lobe hypometabolism on 18F-FDG PET brain scan in unilateral medial temporal lobe epilepsy

Bilateral temporal lobe hypometabolism (BTH) on (18)F-FDG PET brain scan is frequently seen in unilateral medial temporal lobe epilepsy (mTLE). This study aimed to identify the factors that influence BTH in patients with mTLE in order to minimize the significant factor(s) prior to performing a FDG-PET brain scan. Forty patients with unilateral mTLE who underwent (18)F-FDG PET scan for presurgical epilepsy workup were included. Bilateral temporal lobe hypometabolism of the anterior and medial parts of the temporal lobe was identified by a semiquantitative visual scale. Lateralization of TLE was identified by either intracranial EEG (22/40 cases) and/or improvement of seizure 2 years after temporal lobectomy (37/40 cases). The factors analyzed included basic demographic characteristics (age, sex, occupation, years of education, and handedness), history related to seizure (age at epilepsy onset and epilepsy duration, history of febrile seizure and head injury, frequency of seizure with impaired cognition in the last 3 months, presence of secondarily generalized tonic-clonic seizure, automatism side, presence of postictal confusion, and side of MRI temporal abnormality), information during video-EEG monitoring (clinical lateralization, interictal scalp EEG lateralization (interictal epileptiform discharge), and ictal scalp EEG lateralization), and information during the FDG-PET study (duration from the last seizure (≤2 days or >2 days), last seizure type, and the presence of slow waves or sharp waves during the FDG uptake period). Significant factors related to BTH were analyzed using multivariate analysis. Only the ≤2-day duration from the last seizure to the PET scan shows a significant effect (p=0.021) on BTH finding with 15 times greater incidence compared to a duration >2 days. Bilateral temporal lobe hypometabolism, which causes conflict in lateralizing the epileptogenic zone in temporal lobe epilepsy, can be avoided by performing PET scan more than 2 days after the last seizure.

Detection of subcentimeter metastatic cervical lymph node by 18F-FDG PET/CT in patients with well-differentiated thyroid carcinoma and high serum thyroglobulin but negative 131I whole-body scan.

PURPOSE This study aimed to evaluate the diagnostic value of 18F-FDG PET/CT and identify the best parameter to detect subcentimeter cervical nodal metastasis in patients with a well-differentiated thyroid carcinoma (WDTC), elevated serum thyroglobulin (Tg) levels, but negative findings in the 131I whole-body scan (WBS). MATERIALS AND METHODS We prospectively studied 30 consecutive patients with WDTC after standard surgery and radioiodine treatment. All patients had serum Tg greater than 10 ng/mL during thyroid hormone withdrawal but negative findings in the therapeutic 131I WBS. One whole-body CT scan and serial whole-body and neck PET scans were performed between 10 and 170 minutes after 18F-FDG injection. Parameters studied were SUVmax, percent change in SUVmax, SUV ratios of lesions to reference organs, and their percent change. Result in the PET/CT scan was correlated with histopathology and follow-up information. Patient-based and lesion-based (subcentimeter cervical lymph nodes) analyses were performed. Outcome of Tg level after lymph node resection was also analyzed. RESULTS The overall sensitivity, specificity, accuracy, and positive and negative predictive values were 100%, 78%, 93%, 91%, and 100%, respectively. In lesion-based analysis, the differential SUVmax between 2 time points did not provide higher sensitivity than the individual SUVmax at the 60th or 90th minute. A combined SUVmax at the 90th minute greater than 2.75 and a percent change of SUVmax between the 60th and 90th minute greater than -1.1% provides the best diagnostic value with sensitivity, specificity, accuracy, and positive and negative predictive values of 81%, 90%, 83%, 97%, and 56%, respectively. After surgery, patients with completely resected PET-positive nodes without distant metastasis showed reduction of suppressed Tg to less than 2 ng/mL. CONCLUSIONS Combined SUVmax at the 90th minute and the percent change of SUVmax between the 60th and 90th minute provides the best diagnostic value to differentiate benign from malignant conditions in subcentimeter lymph nodes.

PSMA expression by microvasculature of thyroid tumors – Potential implications for PSMA theranostics

Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer epithelium, making it a promising target for molecular imaging and therapy. Recently, several studies found unexpected PSMA radiotracer uptake by thyroid tumors, including radioiodine-refractory (RAIR) cancers. PSMA expression was reported in tumor-associated endothelium of various malignancies, however it has not been systematically addressed in thyroid tumors. We found that PSMA was frequently expressed in microvessels of thyroid tumors (120/267), but not in benign thyroid tissue. PSMA expression in neovasculature was highly irregular ranging from 19% in benign tumors to over 50% in thyroid cancer. Such heterogeneity was not directly attributed to endothelial cell proliferation as confirmed by immunostaining with proliferation-associated endothelial marker CD105. PSMA expression was associated with tumor size (p = 0.02) and vascular invasion in follicular carcinoma (p = 0.03), but not with other baseline histological, and clinical parameters. Significant translational implication is that RAIR tumors and high-grade cancers maintain high level of PSMA expression, and can be targeted by PSMA ligand radiopharmaceuticals. Our study predicts several pitfalls potentially associated with PSMA imaging of the thyroid, such as low expression in oncocytic tumors, absence of organ specificity, and PSMA-positivity in dendritic cells of chronic thyroiditis, which is described for the first time.

Tc-99m pertechnetate scintigraphy to diagnose rectal duplication.

An 8-year-old girl was hospitalized for repeated evaluation for recurrent painless rectal bleeding. Results of the first colonoscopy were normal up to the hepatic flexure. Laboratory evaluations revealed normal prothrombin time, partial prothrombin time, complete blood count, and erythrocyte sedimentation rate. On this admission, results of a Meckels scan were negative for Meckels diverticulum. Repeated colonoscopy revealed a rectal diverticulum 5 cm above the anal verge with mildly inflamed cobblestone mucosa. A review of the Meckels scan showed abnormal uptake in the rectal area. The barium enema showed a duplication of the distal rectum. At surgery, the duplication was found to be 2 cm long and lined by gastric-type epithelium.

Joint reconstruction of Ictal/inter‐ictal SPECT data for improved epileptic foci localization

Purpose To improve the performance for localizing epileptic foci, we have developed a joint ictal/inter‐ictal SPECT reconstruction method in which ictal and inter‐ictal SPECT projections are simultaneously reconstructed to obtain the differential image. Methods We have developed a SPECT reconstruction method that jointly reconstructs ictal and inter‐ictal SPECT projection data. We performed both phantom and patient studies to evaluate the performance of our joint method for epileptic foci localization as compared with the conventional subtraction method in which the differential image is obtained by subtracting the inter‐ictal image from the co‐registered ictal image. Two low‐noise SPECT projection datasets were acquired using 99mTc and a Hoffman head phantom at two different positions and orientations. At one of the two phantom locations, a low‐noise dataset was also acquired using a 99mTc‐filled 3.3‐cm sphere with a cold attenuation background identical to the Hoffman phantom. These three datasets were combined and scaled to mimic low‐noise clinical ictal (three different lesion‐to‐background contrast levels: 1.25, 1.55, and 1.70) and inter‐ictal scans. For each low‐noise dataset, 25 noise realizations were generated by adding Poisson noise to the projections. The mean and standard deviation (SD) of lesion contrast in the differential images were computed using both the conventional subtraction and our joint methods. We also applied both methods to the 35 epileptic patient datasets. Each differential image was presented to two nuclear medicine physicians to localize a lesion and specify a confidence level. The readers’ data were analyzed to obtain the localized‐response receiver operating characteristic (LROC) curves for both the subtraction and joint methods. Results For the phantom study, the difference between the mean lesion contrast in the differential images obtained using the conventional subtraction versus our joint method decreases as the iteration number increases. Compared with the conventional subtraction approach, the SD reduction of lesion contrast at the 10th iteration using our joint method ranges from 54.7% to 68.2% (P < 0.0005), and 33.8% to 47.9% (P < 0.05) for 2 and 4 million total inter‐ictal counts, respectively. In the patient study, our joint method increases the area under LROC from 0.24 to 0.34 and from 0.15 to 0.20 for the first and second reader, respectively. We have demonstrated improved performance of our method as compared to the standard subtraction method currently used in clinical practice. Conclusion The proposed joint ictal/inter‐ictal reconstruction method yields better performance for epileptic foci localization than the conventional subtraction method.